Dual growth factor delivery to achieve therapeutic neovascularization

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This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)0853996SuggsThe goal of the PI is to make a significant contribution in cardiovascular tissue engineering though research, education, and the transformation of stem cell engineering. In this context, stem cell engineering includes the design of cell and drug delivery constructs for regenerative medicine and the elucidation of fundamental scientific principles underlying cell-mediated repair. The objective of this proposal is to create a cell-free, dual growth factor delivery system to recruit endogenous progenitors and promote their long-term survival as well as to test the efficacy of this combination strategy in promoting neovascularization and improving cardiac function. The success of this proposal would enable the PI to establish a program in the area of cardiac engineering with a particular focus on designing cell and drug delivery systems. Cardiac stem cell therapy has demonstrated limited efficacy in clinical trials, but will only become a reality through robust cell engineering processes. This approach has the potential to transform stem cell therapy through harnessing the body's own stem cells. Furthermore, the PI's engineering approach will be used as a platform around which a series of educational and outreach goals will be met.Intellectual Merit: Progress in engineering novel techniques for scaffold synthesis and processing may allow for entry into the new phase of cardiac therapy. Natural and synthetic matrices have shown promise as tools to deliver growth factors and cells; however, to date none of these constructs have exhibited the necessary temporal and spatial control. The combination of delivering multiple growth factors to provide mobilization and survival of resident stem cells in a precisely organized presentation provides a realistic solution to the challenge of cardiac therapy. The PI will investigate whether the system can deliver multiple growth factors with controlled release kinetics. The efficacy of a combination strategy (synergistic stem cell recruitment and sustained cell viability) will be evaluated, and the underlying mechanisms will be explored. Broader Impact: The promise of cardiac regeneration can only be realized through solutions engineered on a molecular and cellular level. It is a goal of the current project to serve two functions: (1) to design a unique delivery platform from which stem cell organization can be controlled and (2) to elucidate fundamental mechanisms underlying cell-mediated cardiac repair. The educational and outreach goals are tightly linked via the ideological concept of engineering design. As a junior faculty, the PI has conceived of and implemented the entire BME senior design sequence at UT Austin. She has a strong and continuing passion for design and its instruction and proposes that design should be integrated at all educational levels. The outreach activities described in this proposal extend from pre-college through the level of the undergraduate student. Specific tools will be developed including teaching modules, online course resources, as well as instructional tools for use by existing pre-college outreach programs.